Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7ADR breast cancer cells

Abstract

The members of the genus Phyllanthus have long been used in the treatment of a broad spectrum of diseases. They exhibited antiproliferative activity against various human cancer cell lines. Breast cancer is the most diagnosed cancer and a leading cause of cancer death among women. Doxorubicin (DOX) is an anticancer agent used to treat breast cancer despite its significant cardiotoxicity along with resistance development. Therefore, this study was designed to assess the potential cytotoxicity of P. niruri extracts (and fractions) alone and in combination with DOX against naïve (MCF-7) and doxorubicin-resistant breast cancer cell lines (MCF-7ADR). The methylene chloride fraction (CH2Cl2) showed the most cytotoxic activity among all tested fractions. Interestingly, the CH2Cl2-fraction was more cytotoxic against MCF-7ADR than MCF-7 at 100 µg/mL. At sub-cytotoxic concentrations, this fraction enhanced the cytotoxic effect of DOX against the both cell lines under investigation (IC50 values of 0.054 µg/mL and 0.14 µg/mL vs. 0.2 µg/mL for DOX alone against MCF-7) and (1.2 µg/mL and 0.23 µg/mL vs. 9.9 µg/mL for DOX alone against MCF-7ADR), respectively. Further, TLC fractionation showed that B2 subfraction in equitoxic combination with DOX exerted a powerful synergism (IC50 values of 0.03 µg/mL vs. 9.9 µg/mL for DOX alone) within MCF-7ADR. Untargeted metabolite profiling of the crude methanolic extract (MeOH) and CH2Cl2 fraction exhibiting potential cytotoxicity was conducted using liquid chromatography diode array detector-quadrupole time-of-flight mass spectrometry (LC-DAD-QTOF). Further studies are needed to separate the active compounds from the CH2Cl2 fraction and elucidate their mechanism(s) of action.

Hypophyllanthin and Phyllanthin from Phyllanthus niruri Synergize Doxorubicin Anticancer Properties against Resistant Breast Cancer Cells

“…From our previous study, only the CH 2 Cl 2 fraction at 100 μg/mL exerted cytotoxic activity against both MCF-7 and MCF-7 ADR cell lines, and it was relatively more cytotoxic against MCF-7 ADR . In addition, the CH 2 Cl 2 fraction at 10 and 100 μg/mL improved the cytotoxic effect of DOX against both cell lines.…”

“… 19 Recently, we investigated the cytotoxic and chemomodulatory effects of crude methanolic extract and several subfractions of P. niruri against MCF-7 and MCF-7 ADR breast cancer cells. 21 The methylene chloride fraction (CH 2 Cl 2 ) showed the most potent cytotoxic activity among all tested fractions. Surprisingly, CH 2 Cl 2 was more cytotoxic against the adriamycin (ADR) multidrug-resistant breast cancer cells (MCF-7 ADR ) when compared to the naïve cells (MCF-7).…”

“…Recently, we investigated the cytotoxic and chemomodulatory effects of crude methanolic extract and several subfractions of P. niruri against MCF-7 and MCF-7 ADR breast cancer cells . The methylene chloride fraction (CH 2 Cl 2 ) showed the most potent cytotoxic activity among all tested fractions.…”

New pyrazolylindolin-2-one based coumarin derivatives as anti-melanoma agents: design, synthesis, dual BRAFV600E/VEGFR-2 inhibition, and computational studies

“…For every sample, the data from 12 000 cells were collected and the distribution of cell cycle phases was analyzed using the ACEA Novo Express™ soware (ACEA Biosciences Inc., San Diego, USA). 64 4.2.5. Apoptosis assay.…”

Synthesis of potent MDA-MB 231 breast cancer drug molecules from single step

“…IC 50 values are greater than 20 for MCF-7 and MDA-MB-231 breast cancer cell lines, IC 50 values greater than 30 for MCF-10A breast cancer cell lines in 24 h incubation period with reference to doxorubicin which is used as a reference drug molecules 34 . IC 50 values for Phyllanthus niuri DCM extract against MCF-7 and MCF-7 ADR breast cancer cell lines showed 100 in 24 h incubation period 35 38 .…”