TY - JOUR
T1 - 3-Methoxy Carbazole Impedes the Growth of Human Breast Cancer Cells by Suppressing NF-κB Signaling Pathway
AU - Alanazi, Jowaher
AU - Unnisa, Aziz
AU - Alanazi, Muteb
AU - Alharby, Tareq Nafea
AU - Moin, Afrasim
AU - Rizvi, Syed Mohd Danish
AU - Hussain, Talib
AU - Awadelkareem, Amir Mahgoub
AU - Elkhalifa, Abd Elmoneim O.
AU - Faiyaz, Syed Shah Mohammed
AU - Khalid, Mohammad
AU - Gowda, Devegowda Vishakante
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.
AB - Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.
KW - 3-Methoxy carbazole
KW - MCF-7 cells
KW - anti-cancer
KW - breast cancer
KW - natural compounds
UR - https://www.scopus.com/pages/publications/85148767407
U2 - 10.3390/ph15111410
DO - 10.3390/ph15111410
M3 - Article
AN - SCOPUS:85148767407
SN - 1424-8247
VL - 15
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 11
M1 - 1410
ER -
