Pair Name	Nobiletin, Vorinostat
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis and autophagy
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Expression	BECN1	hsa8678
	Up-regulation	Expression	BID	hsa637
	Up-regulation	Expression	BIM	hsa10018
	Up-regulation	Cleavage	CASP9	hsa842
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Expression	MCL1	hsa4170
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
In Vitro Model	PC-3	Prostate carcinoma	Homo sapiens (Human)	CVCL_0035
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H69	Lung small cell carcinoma	Homo sapiens (Human)	CVCL_1579
	NCI-H82	Lung small cell carcinoma	Homo sapiens (Human)	CVCL_1591
In Vivo Model	A subcutaneous injection of 5×10⁶ H82 cells was administered into the right flank of each BALB/c nude mouse.
Result	The combination of nobiletin with vorinostat increased histone H3K9 and H3K27 acetylation levels in SCLC mouse tumor tissue and enhanced the expression of the BH3-only proteins BIM and BID. We conclude that nobiletin is a novel natural BH3 mimetic that can cooperate with vorinostat to induce apoptosis and autophagy in SCLC.