Table 3.

Natural substances decrease proliferation in GBM by downregulating upstream growth factors and chemokine ligands, components of the Ras/Raf/MEK/ERK and PI3K/Akt pathways, and downstream effectors.

Effect	Substance	Cell Line	Source
Decreases proliferation/growth	Rutin	C6	[63]
	Quercetin	C6	[63]
	Eucalyptal A	U87MG, LN229	[32]
	Rupesin E	GSC-3#, GSC-18#	[45]
	Crocetin	U87, U138, U251, U373	[34]
	Coronarin D	U251	[47]
	SLCP	U87, U251	[29]
	BBR	U87, U251	[29]
	Tannic Acid	C6	[39]
	Gossypol	Diff13-20, Diff13-18	[30]
	Betulinic Acid	U251, LN229	[48]
	CrataBL	U87	[49]
	Galbanic Acid	U87	[65]
	N45	U87	[66]
	Pisosterol	U87, U343, AHOL1, 1231N1	[60]
Decreases DNA synthesis	CE95	U87	[55]
	CE70	U87, LN-18	[55]
	KW	U87, LN-18	[55]
	KE95	U87, LN-18	[55]
	KE70	U87, LN-18	[55]
	PW	U87	[55]
	PE70	U87	[55]
	RW	U87, LN-18	[55]
	PPE	U87, T98G, LN-18	[57]
	BcH	U87, T98G, LN-18	[57]
Downregulates SRSF1 (mRNA)	Eucalyptal A	U87MG, LN229	[32]
Downregulates SRSF1 (protein)	Eucalyptal A	U87MG, LN229	[32]
Downregulates MYO1B-fl (protein)	Eucalyptal A	U87MG, LN229	[32]
Downregulates p-PDK1 (protein)	Eucalyptal A	U87MG, LN229	[32]
Downregulates TGF (mRNA)	Rutin	U251 orthotopic implants, WR	[63]
	Quercetin	U251 orthotopic implants, WR	[63]
Downregulates TGF-β (mRNA)	Rutin	C6	[63]
	Quercetin	C6	[63]
Downregulates IGF (mRNA)	Rutin	C6, WR-U251 orthotopic implants	[63]
	Quercetin	C6, WR-U251 orthotopic implants	[63]
Downregulates CCL2 (mRNA)	Rutin	U251 orthotopic implants, WR	[63]
	Quercetin	U251 orthotopic implants, WR	[63]
Upregulates CCL5 (mRNA)	Rutin	C6, WR-U251 orthotopic implants	[63]
	Quercetin	C6, WR-U251 orthotopic implants	[63]
Downregulates HDGF (mRNA)	Rutin	C6, WR-U251 orthotopic implants	[63]
	Quercetin	C6, WR-U251 orthotopic implants	[63]
Downregulates GDNF (mRNA)	Rutin	C6, WR-U251 orthotopic implants	[63]
	Quercetin	U251 orthotopic implants, WR	[63]
Downregulates PI3K (protein)	SLCP	U87	[29]
	BBR	U87	[29]
	Diosgenin	C6	[54]
Downregulates (p-)PI3K (protein)	Osthole	MOGGCCM, T98	[64]
	SLCP	U87, U251	[29]
	BBR	U87, U251	[29]
Upregulates AMPK (protein)	Metformin	U87	[67]
Downregulates Akt (mRNA)	Arctigenin	U87MG	[61]
Downregulates Akt (protein)	Cedrol	RG2	[33]
	Metformin	U87, U251	[68]
	SLCP	U87	[29]
	BBR	U87	[29]
Downregulates p-Akt (mRNA)	Arctigenin	U87MG, T98G	[61]
Downregulates p-Akt (protein)	Eucalyptal A	U87MG, LN229	[32]
	Astaxanthin	GL261	[35]
	Adonixanthin	GL261	[35]
	Cedrol	DBTRG-05MG, RG2	[33]
	Arctigenin	U87MG, T98G	[61]
	Xanthohumol	U87	[38]
	CP	GAMG	[36]
	McC1	GAMG, U251	[36]
	SLCP	U87, U251	[29]
	BBR	U87, U251	[29]
	Diosgenin	C6	[54]
Downregulates mTOR (protein)	Metformin	U87	[67]
	SLCP	U87	[29]
	BBR	U87, U251	[29]
Downregulates p-mTOR (mRNA)	Arctigenin	U87MG, T98G	[61]
Downregulates p-mTOR (protein)	Arctigenin	U87MG, T98G	[61]
	SLCP	U87	[29]
	BBR	U87, U251	[29]
	Diosgenin	T98G	[54]
Downregulates Raf (protein)	Osthole	MOGGCCM, T98	[64]
Downregulates c-Myc	Eucalyptal A	U87MG, LN229	[32]
	Xanthohumol	U87, T98G, LN229	[38]
	SLCP	U87	[29]
	BBR	U87	[29]
Downregulates ROS	Astaxanthin	GL261	[35]
	Adonixanthin	GL261	[35]
	Tannic Acid	C6	[39]
Upregulates CAT activity	Tannic Acid	C6	[39]
	BBR	U87	[58]
Upregulates SOD activity	Tannic Acid	C6	[39]
	BBR	U87	[58]
Downregulates JNK (protein)	Cedrol	DBTRG-05MG, RG2	[33]
Downregulates p-JNK (protein)	Cedrol	RG2	[33]
Downregulates p-MEK (protein)	TBMS1	U87, LN229	[41]
Downregulates p-ERK (protein)	Astaxanthin	GL261	[35]
	Adonixanthin	GL261	[35]
	TBMS1	LN229	[41]
Downregulates p38 (protein)	Diosgenin	T98G	[54]
Upregulates p-p38 MAPK (protein)	Astaxanthin	GL261	[35]
	Adonixanthin	GL261	[35]
Downregulates HIF-1α activity	Metformin	U251	[68]
Downregulates NF-κB	Diosgenin	C6, T98G	[54]
Downregulates MET (protein)	TBMS1	U87, LN229	[41]