TY - JOUR
T1 - Antiproliferation for breast cancer cells by ethyl acetate extract of nepenthes thorellii x (Ventricosa x maxima)
AU - Ou-Yang, Fu
AU - Tsai, I. Hsuan
AU - Tang, Jen Yang
AU - Yen, Ching Yu
AU - Cheng, Yuan Bin
AU - Farooqi, Ammad Ahmad
AU - Chen, Shu Rong
AU - Yu, Szu Yin
AU - Kao, Jun Kai
AU - Chang, Hsueh Wei
N1 - Funding Information:
This work was partly supported by funds of the Ministry of Science and Technology (MOST 107-2320-B-037-016, MOST 107-2314-B-037-048, and MOST 107-2311-B-214-003), the National Sun Yatsen University-KMU Joint Research Project (#NSYSUKMU 108-P001), the Kaohsiung Medical University Hospital (KMUH107-7R74), Changhua Christian Hospital-KMU Joint Research Project (108-CCH-KMU-008), the Chimei-KMU jointed project (108CM-KMU-11), the Kaohsiung Medical University Research Center (KMU-TC108A03), and the Health and welfare surcharge of tobacco products, the Ministry of Health and Welfare, Taiwan, Republic of China (MOHW 108-TDU-B-212-124016).
Funding Information:
Funding: This work was partly supported by funds of the Ministry of Science and Technology (MOST 107-2320-B-037-016, MOST 107-2314-B-037-048, and MOST 107-2311-B-214-003), the National Sun Yat-sen University-KMU Joint Research Project (#NSYSUKMU 108-P001), the Kaohsiung Medical University Hospital (KMUH107-7R74), Changhua Christian Hospital-KMU Joint Research Project (108-CCH-KMU-008), the Chimei-KMU jointed project (108CM-KMU-11), the Kaohsiung Medical University Research Center (KMU-TC108A03), and the Health and welfare surcharge of tobacco products, the Ministry of Health and Welfare, Taiwan, Republic of China (MOHW 108-TDU-B-212-124016).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Th.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2′ deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.
AB - Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2′ deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.
KW - Breast cancer
KW - Carnivorous plants
KW - Natural product
KW - Oxidative stress
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U2 - 10.3390/ijms20133238
DO - 10.3390/ijms20133238
M3 - Article
C2 - 31266224
AN - SCOPUS:85068698654
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 13
M1 - 3238
ER -