JOURNAL ARTICLE

The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells

Jung-Hee Kim, Jeong Woo Kang, Man Sub Kim, Yesol Bak, Yun Sun Park, Kang-Yeoun Jung, Yoong Ho Lim, Do-Young Yoon
Toxicology in Vitro: An International Journal Published in Association with BIBRA 2012, 26 (1): 67-73
22056764
This study evaluated the anti-cancer effects of a naringenin derivative in human cervical cancer cells. In this study, a synthesized naringenin derivative, diethyl 5,7,4'-trihydroxy flavanone N-phenyl hydrazone (N101-2), inhibited cervical cancer cell growth, whereas naringenin itself exhibited no anti-cancer activity. N101-2 treatment inhibited cancer cell viability in a dose- and time-dependent manner through cell cycle arrest at sub-G1 phase, accompanied by an increase in apoptotic cell death. Expression of cyclins and ppRB was down-regulated, whereas that of CDK inhibitors and p53 increased upon N101-2 treatment. Meanwhile, we detected processing of caspases-8, -9, and -3, cleavage of PARP, as well as Bax up-regulation, which indicates activation of mitochondria-emanated intrinsic apoptosis signaling. Treatment with caspase-8 and -3 inhibitors also recovered cell cycling, and Fas/FasL expression increased in N101-2-treated cervical cancer cells, suggesting that Fas-mediated extrinsic apoptosis signaling was also activated. The tumor suppressor PTEN and its upstream regulator PPARγ were up-regulated with coincident inhibition of PI3K and phospho-Akt after N101-2 treatment. Taken together, we could conclude that N101-2 induces apoptosis by arresting the cell cycle at sub-G1 phase, activating mitochondria-emanated intrinsic and Fas-mediated extrinsic signaling pathways, and inhibiting the PI3K/AKT pathway in CaSki and SiHa human cervical cancer cells.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
22056764
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"