In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model
Due to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ER...
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/1420-3049/28/23/7701 |
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| author | Jinrong Lin Zhao Qu Huanhuan Pu Li-Sha Shen Xianguo Yi Yu-Shan Lin Rui-Hong Gong Guo-Qing Chen Sibao Chen |
| author_facet | Jinrong Lin Zhao Qu Huanhuan Pu Li-Sha Shen Xianguo Yi Yu-Shan Lin Rui-Hong Gong Guo-Qing Chen Sibao Chen |
| author_sort | Jinrong Lin |
| collection | DOAJ |
| description | Due to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth receptor 2 (HER2). However, clinical chemotherapy for TNBC is marked by its limited efficacy and a pronounced incidence of adverse effects. Consequently, there is a pressing need for novel drugs to treat TNBC. Given the rich repository of diverse natural compounds in traditional Chinese medicine, identifying potential anti-TNBC agents is a viable strategy. This study investigated lasiokaurin (LAS), a natural diterpenoid abundantly present in Isodon plants, revealing its significant anti-TNBC activity both in vitro and in vivo. Notably, LAS treatment induced cell cycle arrest, apoptosis, and DNA damage in TNBC cells, while concurrently inhibiting cell metastasis. In addition, LAS effectively inhibited the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and signal transducer and activator of transcription 3 (STAT3), thus establishing its potential for multitarget therapy against TNBC. Furthermore, LAS demonstrated its ability to reduce tumor growth in a xenograft mouse model without exerting detrimental effects on the body weight or vital organs, confirming its safe applicability for TNBC treatment. Overall, this study shows that LAS is a potent candidate for treating TNBC. |
| first_indexed | 2024-03-09T01:46:34Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T01:46:34Z |
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| series | Molecules |
| spelling | doaj.art-050e110e8b81448f99974b17377fbc742023-12-08T15:22:04ZengMDPI AGMolecules1420-30492023-11-012823770110.3390/molecules28237701In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer ModelJinrong Lin0Zhao Qu1Huanhuan Pu2Li-Sha Shen3Xianguo Yi4Yu-Shan Lin5Rui-Hong Gong6Guo-Qing Chen7Sibao Chen8Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, ChinaThird-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College, China Three Gorges University, Yichang 443002, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, ChinaChongqing Academy of Chinese Materia Medica, Chongqing 400065, ChinaCollege of Animal Science and Technology, Xinyang Agricultural and Forestry University, Xinyang 464000, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, ChinaDepartment of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 999077, ChinaState Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518057, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, ChinaDue to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth receptor 2 (HER2). However, clinical chemotherapy for TNBC is marked by its limited efficacy and a pronounced incidence of adverse effects. Consequently, there is a pressing need for novel drugs to treat TNBC. Given the rich repository of diverse natural compounds in traditional Chinese medicine, identifying potential anti-TNBC agents is a viable strategy. This study investigated lasiokaurin (LAS), a natural diterpenoid abundantly present in Isodon plants, revealing its significant anti-TNBC activity both in vitro and in vivo. Notably, LAS treatment induced cell cycle arrest, apoptosis, and DNA damage in TNBC cells, while concurrently inhibiting cell metastasis. In addition, LAS effectively inhibited the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and signal transducer and activator of transcription 3 (STAT3), thus establishing its potential for multitarget therapy against TNBC. Furthermore, LAS demonstrated its ability to reduce tumor growth in a xenograft mouse model without exerting detrimental effects on the body weight or vital organs, confirming its safe applicability for TNBC treatment. Overall, this study shows that LAS is a potent candidate for treating TNBC.https://www.mdpi.com/1420-3049/28/23/7701lasiokaurinisodontriple-negative breast cancerPI3K/Akt/mTORSTAT3 |
| spellingShingle | Jinrong Lin Zhao Qu Huanhuan Pu Li-Sha Shen Xianguo Yi Yu-Shan Lin Rui-Hong Gong Guo-Qing Chen Sibao Chen In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model Molecules lasiokaurin isodon triple-negative breast cancer PI3K/Akt/mTOR STAT3 |
| title | In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model |
| title_full | In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model |
| title_fullStr | In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model |
| title_full_unstemmed | In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model |
| title_short | In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model |
| title_sort | in vitro and in vivo anti cancer activity of lasiokaurin in a triple negative breast cancer model |
| topic | lasiokaurin isodon triple-negative breast cancer PI3K/Akt/mTOR STAT3 |
| url | https://www.mdpi.com/1420-3049/28/23/7701 |
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