Ganoderma lucidum Fruiting Body Dry Extract inhibits cell proliferation and induces apoptosis in breast cancer cells by activating both caspase-8 and caspase-9.
Year 2023,
, 431 - 439, 30.09.2023
Özge Göktepe
,
Venhar Çınar
,
Zuhal Hamurcu
,
Birkan Yakan
Abstract
Breast cancer is one of the most prominent causes of mortality among women worldwide due to factors such as aggressive behavior of the cancer and resistance to chemotherapeutic agents. Resistance to chemotherapeutic drugs in cancer treatment is a common phenomenon, especially in progressive diseases with a high prevalence. Therefore the current study aimed to demonstrate the anti-cancer effects of GL on MDA-MB-231 and MCF-7 cell lines.
We showed the effect of GL on cell proliferation using the MTS method, its effect on clone formation with a clonogenic test, and we also evaluated whether the apoptotic pathway was activated by western blot.
GL significantly inhibited cell proliferation depending on the dose in MDA-MB-231 and MCF-7 cell lines and it significantly reduced the number of colonies compared to non-treated cells. In addition, GL induced the initiation of apoptosis in MDA-MB-231 and MCF-7 cells, as evidenced by an enhanced level of caspase-8 and caspase-9 and decreased expression of PARP.
These results demonstrated the molecular mechanism underlying the anti-cancer effects of GL, suggesting that GL might be useful in anticancer therapy. Novel products, such as GL, undoubtedly have promise for the future.
Supporting Institution
Erciyes University scientific research projects coordination unit
Project Number
TDK-2018-8349
Thanks
We thank the Erciyes University genome and stem cell center (GENKOK) where the experimental stages of the study took place.
References
- References
- 1. Rodrigues-Ferreire S, Nehlig A, Monchecourt C et al. Combinatorial expression of microtubule-associated EB1 and ATIP3 biomarkers improves breast cancer prognosis. Breast Cancer Research and Treatment 2019;173:573-583. doi: 10.1007/s10549-018-5026-1
- 2. Lee KL, Kuo YC, Ho YS, Huang YH. Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness. Cancers (Basel) 2019;11(9): 1334. doi: 10.3390/cancers11091334
- 3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6): 394-424. doi: 10.3322/caac.21492
- 4. Nakhjavani M, Hardingham JE, Palethorpe HM, Price TJ, Townsend AR. Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer. J Breast Cancer 2019;22(3): 341-361. doi: 10.4048/jbc.2019.22.e39
- 5. Bergin ART, Loi S. Triple-negative breast cancer: recent treatment advances. F1000Res 2019;8: F1000 Faculty Rec-1342. doi: 10.12688/f1000research.18888.1
- 6. Caparica R, Lambertini M, de Azambuja E. How I treat metastatic triple-negative breast cancer. ESMO Open 2019;4: e000504. doi: 10.1136/esmoopen-2019-000504
- 7. El Hachem G, Gombos A, Awada A. Recent advances in understanding breast cancer and emerging therapies with a focus on luminal and triple-negative breast cancer. F1000Res 2019; 8: F1000 Faculty Rev- 591. doi: 10.12688/f1000research.17542.1
- 8. Hwang SY, Park S, Kwon Y. Recent therapeutic trends and promising targets in triple negative breast cancer. Pharmacol Ther 2019;199:30-57. doi: 10.1016/j.pharmthera.2019.02.006
- 9. Paterson RR. Ganoderma a therapeutic fungal biofactory. Photochemistry 2006; 67: 1985-2001. doi: 10.1016/j.phytochem.2006.07.004
- 10. Jin H, Jin F, Jin JX et al. Protective effects of Ganoderma lucidum spore on cadmium hepatotoxicity in mice. Food Chem Toxicol 2013; 52:171–175. doi: 10.1016/j.fct.2012.05.040
- 11. Lu J, Sun LX, Lin ZB et al. Antagonism by Ganoderma lucidum polysaccharides against the suppression by culture supernatants of B16F10 melanoma cells on macrophage. Phytother Res 2014; 28 (2): 200–206. doi: 10.1002/ptr.4980
- 12. Yue QX, Song XY, Ma C et al. Effects of triterpenes from Ganoderma lucidum on protein expression profile of hela cells. Phytomedicine 2010; 17: 606–613. doi: 10.1016/j.phymed.2009
- 13. Jong SC, Donovick R. Antitumor and antiviral substance from fungi. Adv Appl Microbiol 1989; 34: 183-261. doi: 10.1016/s0065-2164(08)70319-8
- 14. Liu RM, Zhong JJ. Ganoderic acid Mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine 2011; 18 (5): 349-355. doi: 10.1016/j.phymed.2010.08.019
- 15. Cör D, Knez Z, Knez Hrnčič M. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review. Molecules 2018; 3(3):649. doi: 10.3390/molecules23030649
- 16. Jiao C, Tan X, Liang H, Li J, Yun H, He C, Chen J, Ma X, Xie Y, Yang BB. Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9. Journal of Ethnopharmacology 2020; 247: 112256. doi: 10.1016/j.jep.2019.112256
- 17. Na K, Li K, Sang T, Wu K, Wang Y, Wang X. Anticarcinogenic effects of water extract of sporoderm-broken spores of Ganoderma lucidum on colorectal cancer in vitro and in vivo. Int J Oncol 2017; 50(5): 1541–1554. doi: 10.3892/ijo.2017.3939
- 18. Yuen JWM, Mak DSY, Chan ES, Gohel MDI, Ng CF. Tumor inhibitory effects of intravesical Ganoderma lucidum instillation in the syngeneic orthotopic MB49/C57 bladder cancer mice model. J Ethnopharmacol 2018;223:113–121. doi: 10.1016/j.jep.2018.05.020
- 19. Jiang J, Slivova V, Sliva D. Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling. Int J Oncol 2006; 29(3): 695-703. doi: 10.3892/ijo.29.3.695
- 20. Wu G, Qian Z, Guo J et al. Ganoderma lucidum extract induces G1 cell cycle arrest, and apoptosis in human breast cancer cells. Am J Chin Med 2012; 40(3): 631-642. doi: 10.1142/S0192415X12500474
- 21. Liu YW, Gao JL, Guan J, Qian ZM, Feng K, Li SP. Evaluation of antiproliferative activities and action mechanisms of extracts from two species of Ganoderma on tumor cell lines. J Agric Food Chem 2009; 57:3087-3093. doi: 10.1021/jf900011f
- 22. Yue GGL, Fung KP, Tse GMK, Leung PC, Lau CBS. Comparative studies of various ganoderma species and their different parts with regard to their antitumor and immunomodulating activities in vitro. J Altern Complement Med 2006; 12:777-789. doi: 10.1089/acm.2006.12.777
- 23. Shi Y, Zheng H, Hong Z, Wang H, Wang Y, Li M, Li Z. Antitumor effects of different Ganoderma lucidum spore powder in cell- and zebrafish-based bioassays. Journal of Integrative Medicine 2021; 19:177-184. doi: 10.1016/j.joim.2021.01.004
- 24. Peto R, Davies C, Godwin J et al. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012; 379(9814): 432-444. doi: 10.1016/S0140-6736(11)61625-5
- 25. Rusu RA, Sirbu D, Curşeu D et al. Chemotherapy-related infectious complications in patients with Hematologic malignancies. J Res Med Sci 2018; 23:68. doi: 10.4103/jrms.JRMS_960_17
- 26. Hatono M, Ikeda H, Suzuki Y et al. Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments. Breast Cancer Research and Treatment 2021; 185(2): 307-316. doi: 10.1007/s10549-020-05957-z
- 27. Kinghorn AD, Carcache de Blanco EJ, Lucas DM, Rakotondraibe HL et al. Discovery of Anticancer Agents of Diverse Natural Origin. Anticancer Res 2016; 36(11): 5623-5637. doi: 10.1351/PAC-CON-08-10-16
- 28. Hsieh TC, Wu CM. Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3. Int J Mol Med 2011; 28(6): 1065-9. doi: 10.3892/ijmm.2011.788
- 29. Martinez-Montemayor MM, Acevedo RR, Otero-Franqui E, Cubano LA, Dharmawardhane SF. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer. Nutr Cancer 2011; 63(7): 1085-1094. doi: 10.1080/01635581.2011.601845
- 30. Guo L, Xie J, Ruan Y et al. Characterization and immunostimulatory activity of a polysaccharide from the spores of Ganoderma lucidum. International Immunopharmacology 2009; 9:1175-1182. doi: 10.1016/j.intimp.2009.06.005
- 31. Huang SQ, Ning ZX. Extraction of polysaccharide from Ganoderma lucidum and its immune enhancement activity. Int J Biol Macromol 2010; 47(3): 336-341. doi: 10.1016/j.ijbiomac.2010.03.019
- 32. Zhao J, Zhang XQ, Li SP, Yang FQ, Wang YT, Ye WC. Quality evaluation of Ganoderma through simultaneous determination of nine triterpenes and sterols using pressurized liquid extraction and high performance liquid chromatography. J Sep Sci 2006; 29(17):2609-2615. doi: 10.1002/jssc.200600178
- 33. Ye WY, Wang JZ, Deng GG, Dang YW, Liu HW, Chen G. Estrogenic activities of compound GL-1, isolated from Ganoderma lucidum. Nat Prod Res 2020; 9:1-5. doi: 10.1080/14786419.2020.1819270
- 34. Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther 2020; 5: 28. doi: 10.1038/s41392-020-0134-x
- 35. Zhong C, Li Y, Li W, lian S, Li Y, Wu C, Zhang K, Zhou G, Wang W, Xu H, Huang M, Katanaev V, Jia L, Lu Y. Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer. Food and Chemical Toxicology 2023; 174: 113654. doi: 10.1016/j.fct.2023.113654
- 36. Hu H, Ahn NS, Yang X, Lee YS, Kang KS. Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int J Cancer 2002; 102: 250–253. doi: 10.1002/ijc.10707
- 37. Kim TH, Kim JS, Kim ZH, Huang RB, Chae YL, Wang RS. Induction of apoptosis in MCF7 human breast cancer cells by khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium). Mol Med Rep 2016; 13: 1243–1249. doi: 10.3892/mmr.2015.4655
- 38. Morales JC, Li L, Fattah FJ et al. Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases. Crit Rev Eukoryat Gene Exp 2014; 24(1): 15-28. doi: 10.1615/critreveukaryotgeneexpr.2013006875
- 39. Chen A. PARP inhibitors: its role in treatment of cancer. Chin J Cancer 2011; 30(7): 463-471. doi: 10.5732/cjc.011.10111
- 40. Drew Y, Calvert H. The potential of PARP inhibitors in genetic breast and ovarian cancers. Ann N Y Acad Sci 2008; 1138:136-145. doi: 10.1196/annals.1414.020
- 41. Slade D. PARP and PARG inhibitors in cancer treatment. Genes Dev 2020; 34:360-394. doi: 10.1101/gad.334516.119
Ganoderma lucidum Fruiting Body Dry Extract, meme kanseri hücre proliferasyonunu inhibe eder ve hem kaspaz-8 hem de kaspaz-9'u aktive ederek apoptozu indükler.
Year 2023,
, 431 - 439, 30.09.2023
Özge Göktepe
,
Venhar Çınar
,
Zuhal Hamurcu
,
Birkan Yakan
Abstract
Meme kanseri, agresif davranışı ve kemoterapötik ajanlara direnç gibi faktörler nedeniyle dünya çapında kadınlar arasında en önemli ölüm nedenlerinden biridir. Kanser tedavisinde kemoterapötik ilaçlara direnç, özellikle prevalansı yüksek olan ilerleyici hastalıklarda sık görülen bir olgudur. Bu nedenle mevcut çalışma, GL'nin MDA-MB-231 ve MCF-7 hücre hatları üzerindeki anti-kanser etkilerini göstermeyi amaçladı.
GL'nin hücre proliferasyonu üzerindeki etkisini MTS yöntemi ile, klon oluşumu üzerindeki etkisini klonojenik test ile gösterdik ve ayrıca apoptotik yolun aktive edilip edilmediği western blot yöntemi ile değerlendirdi.
GL, MDA-MB-231 ve MCF-7 hücre hatlarında doza bağlı olarak hücre proliferasyonunu önemli ölçüde inhibe etti ve tedavi edilmemiş hücrelere kıyasla koloni sayısını önemli ölçüde azalttı. Ek olarak, GL’nin, MDA-MB-231 ve MCF-7 hücrelerinde apoptozu indüklediği artan kaspaz-8 ve kaspaz-9 seviyesi ve azalmış PARP ekspresyonu ile kanıtlandı.
Bu sonuçlar, GL'nin antikanser etkilerinin altında yatan moleküler mekanizmayı gösterdi ve GL'nin antikanser tedavisinde faydalı olabileceğini düşündürdü. GL gibi yeni ürünler şüphesiz gelecek vaat ediyor.
Project Number
TDK-2018-8349
References
- References
- 1. Rodrigues-Ferreire S, Nehlig A, Monchecourt C et al. Combinatorial expression of microtubule-associated EB1 and ATIP3 biomarkers improves breast cancer prognosis. Breast Cancer Research and Treatment 2019;173:573-583. doi: 10.1007/s10549-018-5026-1
- 2. Lee KL, Kuo YC, Ho YS, Huang YH. Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness. Cancers (Basel) 2019;11(9): 1334. doi: 10.3390/cancers11091334
- 3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6): 394-424. doi: 10.3322/caac.21492
- 4. Nakhjavani M, Hardingham JE, Palethorpe HM, Price TJ, Townsend AR. Druggable Molecular Targets for the Treatment of Triple Negative Breast Cancer. J Breast Cancer 2019;22(3): 341-361. doi: 10.4048/jbc.2019.22.e39
- 5. Bergin ART, Loi S. Triple-negative breast cancer: recent treatment advances. F1000Res 2019;8: F1000 Faculty Rec-1342. doi: 10.12688/f1000research.18888.1
- 6. Caparica R, Lambertini M, de Azambuja E. How I treat metastatic triple-negative breast cancer. ESMO Open 2019;4: e000504. doi: 10.1136/esmoopen-2019-000504
- 7. El Hachem G, Gombos A, Awada A. Recent advances in understanding breast cancer and emerging therapies with a focus on luminal and triple-negative breast cancer. F1000Res 2019; 8: F1000 Faculty Rev- 591. doi: 10.12688/f1000research.17542.1
- 8. Hwang SY, Park S, Kwon Y. Recent therapeutic trends and promising targets in triple negative breast cancer. Pharmacol Ther 2019;199:30-57. doi: 10.1016/j.pharmthera.2019.02.006
- 9. Paterson RR. Ganoderma a therapeutic fungal biofactory. Photochemistry 2006; 67: 1985-2001. doi: 10.1016/j.phytochem.2006.07.004
- 10. Jin H, Jin F, Jin JX et al. Protective effects of Ganoderma lucidum spore on cadmium hepatotoxicity in mice. Food Chem Toxicol 2013; 52:171–175. doi: 10.1016/j.fct.2012.05.040
- 11. Lu J, Sun LX, Lin ZB et al. Antagonism by Ganoderma lucidum polysaccharides against the suppression by culture supernatants of B16F10 melanoma cells on macrophage. Phytother Res 2014; 28 (2): 200–206. doi: 10.1002/ptr.4980
- 12. Yue QX, Song XY, Ma C et al. Effects of triterpenes from Ganoderma lucidum on protein expression profile of hela cells. Phytomedicine 2010; 17: 606–613. doi: 10.1016/j.phymed.2009
- 13. Jong SC, Donovick R. Antitumor and antiviral substance from fungi. Adv Appl Microbiol 1989; 34: 183-261. doi: 10.1016/s0065-2164(08)70319-8
- 14. Liu RM, Zhong JJ. Ganoderic acid Mf and S induce mitochondria mediated apoptosis in human cervical carcinoma HeLa cells. Phytomedicine 2011; 18 (5): 349-355. doi: 10.1016/j.phymed.2010.08.019
- 15. Cör D, Knez Z, Knez Hrnčič M. Antitumour, Antimicrobial, Antioxidant and Antiacetylcholinesterase Effect of Ganoderma Lucidum Terpenoids and Polysaccharides: A Review. Molecules 2018; 3(3):649. doi: 10.3390/molecules23030649
- 16. Jiao C, Tan X, Liang H, Li J, Yun H, He C, Chen J, Ma X, Xie Y, Yang BB. Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9. Journal of Ethnopharmacology 2020; 247: 112256. doi: 10.1016/j.jep.2019.112256
- 17. Na K, Li K, Sang T, Wu K, Wang Y, Wang X. Anticarcinogenic effects of water extract of sporoderm-broken spores of Ganoderma lucidum on colorectal cancer in vitro and in vivo. Int J Oncol 2017; 50(5): 1541–1554. doi: 10.3892/ijo.2017.3939
- 18. Yuen JWM, Mak DSY, Chan ES, Gohel MDI, Ng CF. Tumor inhibitory effects of intravesical Ganoderma lucidum instillation in the syngeneic orthotopic MB49/C57 bladder cancer mice model. J Ethnopharmacol 2018;223:113–121. doi: 10.1016/j.jep.2018.05.020
- 19. Jiang J, Slivova V, Sliva D. Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling. Int J Oncol 2006; 29(3): 695-703. doi: 10.3892/ijo.29.3.695
- 20. Wu G, Qian Z, Guo J et al. Ganoderma lucidum extract induces G1 cell cycle arrest, and apoptosis in human breast cancer cells. Am J Chin Med 2012; 40(3): 631-642. doi: 10.1142/S0192415X12500474
- 21. Liu YW, Gao JL, Guan J, Qian ZM, Feng K, Li SP. Evaluation of antiproliferative activities and action mechanisms of extracts from two species of Ganoderma on tumor cell lines. J Agric Food Chem 2009; 57:3087-3093. doi: 10.1021/jf900011f
- 22. Yue GGL, Fung KP, Tse GMK, Leung PC, Lau CBS. Comparative studies of various ganoderma species and their different parts with regard to their antitumor and immunomodulating activities in vitro. J Altern Complement Med 2006; 12:777-789. doi: 10.1089/acm.2006.12.777
- 23. Shi Y, Zheng H, Hong Z, Wang H, Wang Y, Li M, Li Z. Antitumor effects of different Ganoderma lucidum spore powder in cell- and zebrafish-based bioassays. Journal of Integrative Medicine 2021; 19:177-184. doi: 10.1016/j.joim.2021.01.004
- 24. Peto R, Davies C, Godwin J et al. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012; 379(9814): 432-444. doi: 10.1016/S0140-6736(11)61625-5
- 25. Rusu RA, Sirbu D, Curşeu D et al. Chemotherapy-related infectious complications in patients with Hematologic malignancies. J Res Med Sci 2018; 23:68. doi: 10.4103/jrms.JRMS_960_17
- 26. Hatono M, Ikeda H, Suzuki Y et al. Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments. Breast Cancer Research and Treatment 2021; 185(2): 307-316. doi: 10.1007/s10549-020-05957-z
- 27. Kinghorn AD, Carcache de Blanco EJ, Lucas DM, Rakotondraibe HL et al. Discovery of Anticancer Agents of Diverse Natural Origin. Anticancer Res 2016; 36(11): 5623-5637. doi: 10.1351/PAC-CON-08-10-16
- 28. Hsieh TC, Wu CM. Suppression of proliferation and oxidative stress by extracts of Ganoderma lucidum in the ovarian cancer cell line OVCAR-3. Int J Mol Med 2011; 28(6): 1065-9. doi: 10.3892/ijmm.2011.788
- 29. Martinez-Montemayor MM, Acevedo RR, Otero-Franqui E, Cubano LA, Dharmawardhane SF. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer. Nutr Cancer 2011; 63(7): 1085-1094. doi: 10.1080/01635581.2011.601845
- 30. Guo L, Xie J, Ruan Y et al. Characterization and immunostimulatory activity of a polysaccharide from the spores of Ganoderma lucidum. International Immunopharmacology 2009; 9:1175-1182. doi: 10.1016/j.intimp.2009.06.005
- 31. Huang SQ, Ning ZX. Extraction of polysaccharide from Ganoderma lucidum and its immune enhancement activity. Int J Biol Macromol 2010; 47(3): 336-341. doi: 10.1016/j.ijbiomac.2010.03.019
- 32. Zhao J, Zhang XQ, Li SP, Yang FQ, Wang YT, Ye WC. Quality evaluation of Ganoderma through simultaneous determination of nine triterpenes and sterols using pressurized liquid extraction and high performance liquid chromatography. J Sep Sci 2006; 29(17):2609-2615. doi: 10.1002/jssc.200600178
- 33. Ye WY, Wang JZ, Deng GG, Dang YW, Liu HW, Chen G. Estrogenic activities of compound GL-1, isolated from Ganoderma lucidum. Nat Prod Res 2020; 9:1-5. doi: 10.1080/14786419.2020.1819270
- 34. Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther 2020; 5: 28. doi: 10.1038/s41392-020-0134-x
- 35. Zhong C, Li Y, Li W, lian S, Li Y, Wu C, Zhang K, Zhou G, Wang W, Xu H, Huang M, Katanaev V, Jia L, Lu Y. Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer. Food and Chemical Toxicology 2023; 174: 113654. doi: 10.1016/j.fct.2023.113654
- 36. Hu H, Ahn NS, Yang X, Lee YS, Kang KS. Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int J Cancer 2002; 102: 250–253. doi: 10.1002/ijc.10707
- 37. Kim TH, Kim JS, Kim ZH, Huang RB, Chae YL, Wang RS. Induction of apoptosis in MCF7 human breast cancer cells by khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium). Mol Med Rep 2016; 13: 1243–1249. doi: 10.3892/mmr.2015.4655
- 38. Morales JC, Li L, Fattah FJ et al. Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases. Crit Rev Eukoryat Gene Exp 2014; 24(1): 15-28. doi: 10.1615/critreveukaryotgeneexpr.2013006875
- 39. Chen A. PARP inhibitors: its role in treatment of cancer. Chin J Cancer 2011; 30(7): 463-471. doi: 10.5732/cjc.011.10111
- 40. Drew Y, Calvert H. The potential of PARP inhibitors in genetic breast and ovarian cancers. Ann N Y Acad Sci 2008; 1138:136-145. doi: 10.1196/annals.1414.020
- 41. Slade D. PARP and PARG inhibitors in cancer treatment. Genes Dev 2020; 34:360-394. doi: 10.1101/gad.334516.119