1. Nelfinavir in Cancer
Tomas Koltai M.D.

2. HIV PROTEASE INHIBITORS
Ritonavir
Saquinavir
Nelfinavir
HIV PROTEASE INHIBITORS
GROWTH ARREST
APOPTOSIS
Blockade of Interleukin 6
Phosphorilation of
STAT 3 and ERK ½
HIV-1 protease inhibitor induces
Growth arrest and apoptosis of
human multiple myeloma cells
via inactivation of signal
transducer and activator of
transcription 3 and
extracellular signal-regulated
kinase 1/2
Takayuki Ikezoe,
Tsuyako Saito,
Kentaro Bandobashi,
Yang Yang,
H. Phillip Koeffler and
Hirokuni Taguchi
Mol Cancer Ther. 2004 Apr;3(4):473-9.
Multiple myeloma

3. HIV PROTEASE INHIBITORS
Nelfinavir
HIV PROTEASE INHIBITORS
GROWTH ARREST
APOPTOSIS
Downregulation of Akt
NFV, an HIV-1 protease inhibitor,
induces growth arrest, reduced Akt
signalling, apoptosis and docetaxel
sensitisation in NSCLC cell lines.
Yang Y, Ikezoe T, Nishioka C,
Bandobashi K, Takeuchi T, Adachi Y,
Kobayashi M, Takeuchi S, Koeffler HP,
Taguchi H.
Br J Cancer. 2006; 18;95(12):
NSCLC cell lines

4. HIV PROTEASE INHIBITORS
Ritonavir
Saquinavir
Nelfinavir
HIV PROTEASE INHIBITORS
INHIBITION OF BCRP
J Pharmacol Exp Ther. 2004
Jul;310(1):334-41
HIV protease inhibitors are inhibitors
but not substrates of the human breast 
cancer resistance protein
(BCRP/ABCG2).
Gupta A1, Zhang Y, Unadkat JD, Mao Q.
breast

5. HIV PROTEASE INHIBITORS
Nelfinavir
GROWTH ARREST
INHIBITION OF AKT
APOPTOSIS
INHIBITION OF STAT3
INHIBITION OF
ANDROGEN RECEPTOR
SIGNALING
HIV-1 protease inhibitor induces growth
arrest and apoptosis of human prostate 
cancer LNCaP cells in vitro and in vivo in
conjunction with blockade of androgen
receptor STAT3 and AKT signaling.
Yang Y, Ikezoe T, Takeuchi T, Adachi Y,
Ohtsuki Y, Takeuchi S, Koeffler HP,
Taguchi H.
Cancer Sci Jul;96(7):
prostate

6. HIV PROTEASE INHIBITORS
Nelfinavir
GROWTH ARREST (G1)
APOPTOSIS
Inhibition of CDK2
through proteasome
degradation
HIV protease inhibitor nelfinavir 
inhibits growth of human melanoma
cells by induction of cell cycle arrest.
Jiang W, Mikochik PJ, Ra JH, Lei H,
Flaherty KT, Winkler JD, Spitz FR.
Cancer Res Feb 1;67(3):
Melanoma cells

7. HIV PROTEASE INHIBITORS
Ritonavir
Saquinavir
Nelfinavir
HIV PROTEASE INHIBITORS
RADIOSENSITIZATION
INHIBITION OF AKT
IV protease inhibitors block Akt signaling
and radiosensitize tumor cells both in vitro
and in vivo.
Gupta AK, Cerniglia GJ, Mick R,
McKenna WG, Muschel RJ.
Cancer Res Sep 15;
65(18):
MR4 cells

8. HIV PROTEASE INHIBITORS
Nelfinavir
CELL CYCLE ARREST
APOPTOSIS
INHIBITION OF SREBP1
Nelfinavir induces liposarcoma
apoptosis and cell cycle arrest
by upregulating sterol
regulatory element binding protein-1.
Chow WA, Guo S, Valdes-Albini F.
Anticancer Drugs Sep;17(8):
Liposarcoma

9. HIV PROTEASE INHIBITORS
Nelfinavir
Amprenavir
ANTIANGIOGENESIS
Downregulation of Akt
Downregulation of HIF
Downregulation of VEGF
HIV protease inhibitors decrease
VEGF/HIF-1 alfa expression and
angiogenesis in glioblastoma cells
Pore N, Gupta AK, Cerniglia GJ, Maity A
Neoplasia (11):
Glioblastoma

10. HIV PROTEASE INHIBITORS
Nelfinavir
RADIOSENSITIZATION
ANTIANGIOGENESIS
Downregulation of HIF 1 alfa
Downregulation of VEGF
Squamous cell carcinoma cells
Lung carcinoma cells
Nelfinavir down-regulates hypoxia-
Inducible factor 1alpha and VEGF
expression and increases tumor
oxygenation: implications
for radiotherapy.
Pore N, Gupta AK, Cerniglia GJ, Jiang Z,
Bernhard EJ, Evans SM, Koch CJ,
Hahn SM, Maity A.
Cancer Res Sep 15;66(18):

11. HIV PROTEASE INHIBITORS
Nelfinavir
GROWTH INHIBITION
APOPTOSIS
Akt inhibition
Autophagy
Endoplasmic Reticulum Stress
Lung carcinoma cells
NSCLC
Nelfinavir a lead HIV protease inhibitor
Is a broad spectrum anticancer agent
That induces endoplasmic reticulum stress,
Autophagy and apoptosis in vitro and
In vivo.
Gills JJ, Lo Piccolo J, Tsurutani J
Et al.
Clin Cancer Res. 2007;13:

12. HIV PROTEASE INHIBITORS
Nelfinavir
POTENTIATION OF IMATINIB
APOPTOSIS
Decrease in survivin
Nelfinavir potentiation of imatinib
cytotoxicity in meningioma cells via
survivin inhibition.
Gupta V, Samuleson CG, Su S, Chen TC.
Neurosurg Focus. 2007;23(4):E9.
Meningioma

13. HIV PROTEASE INHIBITORS
Nelfinavir
Atazanavir
Inhibition of proteasome activity
Endoplasmic Reticulum Stress (ERS)
APOPTOSIS
Glioblastoma
HIV protease inhibiors Nelfinavir and
Atazanavir induce malignant glioma death
By Triggering endoplasmic reticulum
stress
Pyrko P, Kardosh A, Wang W. et al
Cancer Res. 2007;67:
Nelfinavir
ERS
INHIBITION OF
PROTEASOME
CELL
DEATH
Misfolded protein
accumulation

14. Nelfinavir and atazanavir cause inhibition of the proteasome
Nelfinavir and atazanavir cause inhibition of the proteasome. A, U251 glioblastoma cells were grown in the presence of 50 μmol/L
nelfinavir for 24 h and visualized by light microscopy. Arrows, point to dilated ER cisternae. B, U251 cells in the presence of 50 μmol/L nelfinavir for 24 h were visualized by transition electron microscopy. Left, majority of the cell. Right, close-up on a part of
the cell that contains an aggresome (arrows and inset). C, U251 cells were cultured in the presence or absence of 50 μmol/L nelfinavir and 80 μmol/L atazanavir for 24 h. Cellular lysates were prepared and subjected to Western blot analysis with antibodies
to ubiquitin.

15. Nelfinavir ERS Misfolded protein accumulation STAT 3 Inhibition Akt
INHIBITION OF
PROTEASOME
Nelfinavir
ERS
Misfolded protein
accumulation
STAT 3
Inhibition
Akt
inhibition
ERK ½
inhibition
CELL
DEATH
GROWTH
ARREST
HIDROXYCHLOROQUINE
AUTOPHAGY